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Literature summary extracted from

  • Sheng, C.; Miao, Z.; Ji, H.; Yao, J.; Wang, W.; Che, X.; Dong, G.; Lue, J.; Guo, W.; Zhang, W.
    Three-dimensional model of lanosterol 14 alpha-demethylase from Cryptococcus neoformans: active-site characterization and insights into azole binding (2009), Antimicrob. Agents Chemother., 53, 3487-3495.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.14.154 additional information active site with four functional regions Cryptococcus neoformans

Application

EC Number Application Comment Organism
1.14.14.154 drug development structural model of CYP51 can be used in azole optimization, virtual screening, or de novo inhibitor design for the discovery of new antifungal agents Cryptococcus neoformans

Protein Variants

EC Number Protein Variants Comment Organism
1.14.14.154 G484S azole resistance Cryptococcus neoformans

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.14.154 albaconazole lower interaction energies with CYP51 than those of voriconazole Cryptococcus neoformans
1.14.14.154 fluconazole is bound to the active site of CYP51 through the formation of a coordination bond with the iron of the heme group (the P1 subsite). The difluorophenyl group of fluconazole points toward substrate access channel 1 (the BC loop) and forms a hydrophobic interaction with Met153 and the alkyl group of Lys157 (the P3 subsite). Another triazolyl ring of fluconazole attached to C-3 has a preferable orientation toward substrate access channel 2 (the FG loop) and forms indirect nonbonding interactions with the surrounding residues, lined with Leu134, Phe240, Met316, Ile386, and Ile529 (the P4 subsite). The hydroxyl group attached to C-2 is important for antifungal activity, but no interaction between this hydroxyl group and the active site of CYP51 Cryptococcus neoformans
1.14.14.154 itraconazole lowest interaction energies with CYP51 Cryptococcus neoformans
1.14.14.154 posaconazole lowest interaction energies with CYP51 Cryptococcus neoformans
1.14.14.154 ravuconazole thiazole ring interacts with the side chain of Tyr131, Leu134, and Ile389. Besides the hydrophobic interaction with Phe240, Met528, and Ile529, the 4-cyano-phenyl group of ravuconazole can also form a pi-pi stacking interaction with His133 Cryptococcus neoformans
1.14.14.154 voriconazole shows higher affinity with CYP51 than fluconazole Cryptococcus neoformans

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.14.154 Iron
-
 Cryptococcus neoformans

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.154 Cryptococcus neoformans Q870D1
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.154 24(28)-methylene-24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Cryptococcus neoformans 4,4-dimethyl-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.14.154 CYP51
-
 Cryptococcus neoformans